Solution-phase parallel synthesis and biological evaluation of combretatriazoles

Laura Cafici; Tracey Pirali; Fabrizio Condorelli; Erika Del Grosso; Alberto Massarotti; Giovanni Sorba; Pier Luigi Canonico; Gian Cesare Tron; Armando A. Genazzani

doi:10.1021/cc800090d

Solution-phase parallel synthesis and biological evaluation of combretatriazoles

Laura Cafici, Tracey Pirali, Fabrizio Condorelli, Erika Del Grosso, Alberto Massarotti, Giovanni Sorba, Pier Luigi Canonico, Gian Cesare Tron, Armando A. Genazzani

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins containing a triazole ring (combretatriazoles). To achieve this, we have developed a column chromatography-free parallel solution-phase synthesis that exploits the reaction between azides and α-keto phosphorus ylids, which is known to regioselectively generate the 1,5-disubstituted triazoles. The prepared compounds were screened as antitubulinic agents, allowing us to identify three new compounds with high potency, two of which show a new mechanism of action that induces cells to appear multinucleated and display a high number of mitotic spindles.

Original language	English
Pages (from-to)	732-740
Number of pages	9
Journal	Journal of Combinatorial Chemistry
Volume	10
Issue number	5
DOIs	https://doi.org/10.1021/cc800090d
Publication status	Published - Sept 2008

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abstract = "Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins containing a triazole ring (combretatriazoles). To achieve this, we have developed a column chromatography-free parallel solution-phase synthesis that exploits the reaction between azides and α-keto phosphorus ylids, which is known to regioselectively generate the 1,5-disubstituted triazoles. The prepared compounds were screened as antitubulinic agents, allowing us to identify three new compounds with high potency, two of which show a new mechanism of action that induces cells to appear multinucleated and display a high number of mitotic spindles.",

author = "Laura Cafici and Tracey Pirali and Fabrizio Condorelli and {Del Grosso}, Erika and Alberto Massarotti and Giovanni Sorba and Canonico, {Pier Luigi} and Tron, {Gian Cesare} and Genazzani, {Armando A.}",

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T1 - Solution-phase parallel synthesis and biological evaluation of combretatriazoles

AU - Cafici, Laura

AU - Pirali, Tracey

AU - Condorelli, Fabrizio

AU - Del Grosso, Erika

AU - Massarotti, Alberto

AU - Sorba, Giovanni

AU - Canonico, Pier Luigi

AU - Tron, Gian Cesare

AU - Genazzani, Armando A.

PY - 2008/9

Y1 - 2008/9

N2 - Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins containing a triazole ring (combretatriazoles). To achieve this, we have developed a column chromatography-free parallel solution-phase synthesis that exploits the reaction between azides and α-keto phosphorus ylids, which is known to regioselectively generate the 1,5-disubstituted triazoles. The prepared compounds were screened as antitubulinic agents, allowing us to identify three new compounds with high potency, two of which show a new mechanism of action that induces cells to appear multinucleated and display a high number of mitotic spindles.

AB - Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins containing a triazole ring (combretatriazoles). To achieve this, we have developed a column chromatography-free parallel solution-phase synthesis that exploits the reaction between azides and α-keto phosphorus ylids, which is known to regioselectively generate the 1,5-disubstituted triazoles. The prepared compounds were screened as antitubulinic agents, allowing us to identify three new compounds with high potency, two of which show a new mechanism of action that induces cells to appear multinucleated and display a high number of mitotic spindles.

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Solution-phase parallel synthesis and biological evaluation of combretatriazoles

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